What is Heredity? G E N E T I C S. Heredity is the passing of traits from parents to offspring

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1 G E N E T I C S A wild carrot has a small, tough, pale, bitter white root; while modern domestic carrots Usually have a swollen, sweet, orange root. Carrots originated in present day Afghanistan about 5000 years ago, probably originally as a purple or yellow root. Purple, white and yellow carrots were imported to southern Europe in the 14th century and were widely grown in Europe into the 17th Century. The Dutch growers developed them to be sweeter, more practical and more orange. Finally we have the French to thank for popular modern varieties, with credit to the 19th century horticulturist Louis de Vilmorin, who laid the foundations for modern plant breeding. Selective Breeding is the process by which humans choose the traits they find most desirable and allow only those individuals to reproduce. What is Heredity? Heredity is the passing of traits from parents to offspring 1

2 How did you get your traits? Half of your genes (on chromosomes) came from your mom, and half from your dad. This gives each person a unique genetic code. What is Genetics? Genetics is the Study of Heredity Why Is Your Combination of Genes/Traits Unique? When the egg and sperm were formed during meiosis, crossing over and independent assortment mixed up your genes, giving you a one-of-a-kind genotype. In addition genetic recombination as a result of sexual reproduction (egg + sperm = zygote), is all based on random chance. This is what creates variation which drives the process of evolution. 2

3 Every day we observe variations among individuals in a population. (human eyes vary from brown, green, blue, to gray) We already know how these traits are transmitted from parents to offspring but how does your body decide what color eyes to have? The History of Genetics (or all the section of the notes where we talk about all the silly things people used to think were true) The Blending Hypothesis. This hypothesis proposed that the genetic material contributed by each parent mixes in a manner analogous to the way blue and yellow paint blend to make green. 3

4 Under the blending system we would expect to see large populations of uniform individuals. For example blue and brown eyed parents should have children with eyes that are whatever color is blue and brown mixed together 4

5 The problem with blending is that eventually everyone would have the same color eyes The blending hypothesis is shown to be incorrect by everyday observations Parents with brown and blue eyes usually have brown eyed offspring The results of breeding experiments also contradict blending predictions. An alternative to the blending model is called particulate inheritance. Particulate Inheritance proposes that parents pass on discrete heritable units - called genes - that retain their separate identities in offspring. 5

6 In particulate inheritance genes can be sorted and passed on, generation after generation, in an unmixed form. Modern genetics began in an abbey garden, where a monk names Gregor Mendel documented the particulate mechanism of inheritance. Mendel grew up on a small farm in what is today the Czech Republic. In 1843, Mendel entered an Augustinian monastery. He studied at the University of Vienna from 1851 to 1853 where he was influenced by a physicist who encouraged experimentation and the application of mathematics to science and by a botanist who aroused Mendel s interest in the causes of variation in plants. These influences came together in Mendel s experiments. Mendel Father of Genetics After the university, Mendel taught at the Brunn Modern School and lived in the local monastery. The monks at this monastery had a long tradition of interest in the breeding of plants, including peas. Around 1857, Mendel began breeding garden peas to study inheritance. Pea plants have several advantages for genetics. Pea plants are available in many varieties with distinct heritable features (characters) with different variants (traits). 6

7 In 1865 Mendel announced his findings about the laws of heredity, resulting from eight years of study on pea plants and their traits. But nobody noticed Unfortunately because he published in the wrong language Mendel s work was not appreciated by scientists until 1900, sixteen years after his death. Today Mendel s Laws of Heredity are the basis of modern genetics. They are the Laws of Dominance, Segregation, Independent Assortment. Another advantage of peas is that Mendel had strict control over which plants mated with which. Each pea plant has male and female sexual organs. In nature, pea plants typically self-fertilize, fertilizing ova with their own sperm. However, Mendel could also move pollen from one plant to another to crosspollinate plants. 7

8 In a typical breeding experiment, Mendel would crosspollinate (hybridize) two contrasting, true-breeding pea varieties. Parents are called the P generation Their offspring are called the F 1 generation. Mendel would then allow the F 1 hybrids to self-pollinate to produce an F 2 generation. It was mainly Mendel s quantitative analysis of F 2 plants that revealed the two fundamental principles of heredity: the law of segregation and the law of independent assortment. By the law of segregation, the two alleles for a character are packaged into separate gametes If the blending model were correct, the F 1 hybrids from a cross between purple-flowered and whiteflowered pea plants would have pale purple flowers. Instead, the F 1 hybrids all have purple flowers, just as purple as the purple-flowered parents. 8

9 When Mendel allowed the F 1 plants to selffertilize, the F 2 generation included both purpleflowered and white-flowered plants. The white trait, absent in the F 1, reappeared in the F 2. This cross produced a three purple to one white ratio of traits in the F 2 offspring. Mendel reasoned that the heritable factor for white flowers was present in the F 1 plants, but it did not affect flower color. Purple flower color is a dominant trait and white flower color is a recessive trait. The reappearance of whiteflowered plants in the F 2 generation indicated that the heritable factor for the white trait was not diluted or blended by coexisting with the purple-flower factor in F 1 hybrids. 9

10 Mendel found similar 3 to 1 ratios of two traits among F 2 offspring when he conducted crosses for six other characters, each represented by two different varieties. For example, when Mendel crossed two truebreeding varieties, one of which produced round seeds, the other of which produced wrinkled seeds All the F 1 offspring had round seeds The F 2 plants, 75% of the seeds were round and 25% were wrinkled. 10

11 Mendel developed a hypothesis to explain these results that consisted of four related ideas. 1. Alternative versions of genes (different alleles) account for variations in inherited characters. Different alleles vary somewhat in the sequence of nucleotides at the specific locus of a gene. The purple-flower allele and white-flower allele are two DNA variations at the flower-color locus. 2. For each character, an organism inherits two alleles, one from each parent. A diploid organism inherits one set of chromosomes from each parent. Each diploid organism has a pair of homologous chromosomes and therefore two copies of each locus. These homologous loci may be identical or the two alleles may differ. In the flower-color example, the F 1 plants inherited a purple-flower allele from one parent and a white-flower allele from the other. 3. If two alleles differ, then one, the dominant allele, is fully expressed in the organism s appearance. The other, the recessive allele, has no noticeable effect on the organism s appearance. Mendel s F 1 plants had purple flowers because the purple-flower allele is dominant and the white-flower allele is recessive. 11

12 4. The two alleles for each character segregate (separate) during gamete production. This segregation of alleles corresponds to the distribution of homologous chromosomes to different gametes in meiosis. If an organism has identical alleles for a particular character, then that allele exists as a single copy in all gametes. If different alleles are present, then 50% of the gametes will receive one allele and 50% will receive the other. The separation of alleles into separate gametes is summarized as Mendel s law of segregation. Mendel s law of segregation accounts for the 3:1 ratio observed in the F 2 generation. The F 1 hybrids will produce two classes of gametes, half with the purple-flower allele (P) and half with the white-flower allele (p). During self-pollination, the gametes of these two classes unite randomly. 12

13 A Punnett square predicts the results of a genetic cross between individuals of known genotype. This can produce four equally likely combinations of sperm and ovum. (PP) (Pp)(Pp)(pp) A Punnett square analysis of the flower-color example demonstrates Mendel s model. One in four F 2 offspring will inherit two white-flower alleles and produce white flowers. (pp) Half of the F 2 offspring will inherit one white-flower allele and one purple-flower allele and produce purple flowers. (Pp) One in four F 2 offspring will inherit two purple-flower alleles and produce purple flowers too. (PP) An organism with two identical alleles for a character is homozygous for that character. TT homozygous dominant tt homozygous recessive 13

14 Organisms with two different alleles for a characteristic is heterozygous for that trait. Tt heterozygous A description of an organism s traits is its phenotype. A description of an organism s genetic makeup is its genotype. 14

15 MENDEL AND THE GENE IDEA - Segregation, the two alleles for a character are packaged into separate gametes - Independent assortment, each pair of alleles segregates into gametes independently - Dominance, some alleles are more powerful then other (recessive) alleles Mendelian inheritance reflects rules of probability Mendel discovered the particulate behavior of genes For flower color in peas, both PP and Pp plants have the same phenotype (purple) but different genotypes (homozygous and heterozygous). The only way to produce a white phenotype is to be homozygous recessive (pp) for the flowercolor gene. It is not possible to predict the genotype of an organism with a dominant phenotype. The organism must have one dominant allele, but it could be homozygous dominant or heterozygous. A testcross, breeding a homozygous recessive with dominant phenotype, but unknown geneotype, can determine the identity of the unknown allele. 15

16 Cross a Heterozygous Axial Flower with a Terminal Cross a Heterozygous Axial flower with a Terminal flower The first step is to define your variables: A = Axial a = Terminal Cross a Heterozygous Axial flower with a Terminal flower A = Axial a= Terminal The second step is to define the parent genotypes Heterozygous Axial = Aa Terminal = aa 16

17 Cross a Heterozygous Axial flower with a Terminal flower Heterozygous Axial = Aa Terminal = aa A = Axial a= Terminal Third step is to load the gametes onto the outside of the Punnett square a a A a Cross a Heterozygous Axial flower with a Terminal flower Heterozygous Axial = Aa Terminal = aa A = Axial a= Terminal Fourth step is to load the inner cells with the gametes to predict the possible zygotes 1 st do one set of gametes A a a A a a A a Cross a Heterozygous Axial flower with a Terminal flower Heterozygous Axial = Aa Terminal = aa A = Axial a= Terminal Fourth step is to load the inner cells with the gametes to predict the possible zygotes Then do the other A a a Aa aa a Aa aa 17

18 Cross a Heterozygous Axial flower with a Terminal flower Heterozygous Axial = Aa Terminal = aa A = Axial a= Terminal The fifth step is to count the zygotes and make ratios Genotype 50% Aa 50% aa Phenotype 50% Axial 50% terminal A a a Aa aa a Aa aa Cross a Homozygous Yellow seed with a Heterozygous seed Cross a Homozygous Yellow seed with a Heterozygous seed Homozygous = YY Heterozygous = Yy Y Y Y = Yellow y= green Y y YY Yy YY Yy Genotype: 50% YY 50% Yy Phenotype: 100% Yellow 18

19 Cross Two Heterozygous Yellow Seeds Cross a Two Heterozygous Yellow seeds Heterozygous = Yy Heterozygous = Yy Y y Y = Yellow y= green Y y YY Yy Yy yy Genotype: 25% YY 50% Yy 25% yy Phenotype: 75% Yellow 25% Green If the occurrence of widows peak (W) is dominant to a straight hairline (w) then Cross a Female who is heterozygous for widows peak with a male who has a straight hairline. 19

20 Cross a Female who is heterozygous for widows peak with a male who has a straight hairline. Heterozygous = Ww Homozygous Recessive = ww w w W Ww Ww W = Widows Peak w= straight hairline w ww ww Genotype: 50% Ww 50% ww Phenotype: 50% Peak 50% Straight Tongue rolling is dominant To no rolling or is it? Most people, when first asked, either can easily roll their tongue (here called "R"), or cannot roll it at all ("NR"). The proportion of people who can roll their tongue ranges from 65 to 81 percent, with a slightly higher proportion of tongue-rollers in females than in males. Komai (1951) Parents R offspring NR offspring Percent R R x R % R x NR % NR x NR % Family studies clearly demonstrate that tongue rolling is not a simple genetic character, and twin studies demonstrate that it is influenced by both genetics and the environment. Despite this, tongue rolling is probably the most commonly used classroom example of a simple genetic trait in humans. 20

21 If tongue rolling was a simple dominant and recessive trait what would happen if a female who is homozygous dominant crosses with a male who is homozygous recessive? Homozygous Dominant = TT Homozygous Recessive = tt t t T Tt Tt T Tt Tt T = can roll t = can t roll Genotype: 100% Tt Phenotype: 100% Rolls Some people have earwax that is wet, sticky and yellow or brown; other people's earwax is dry, crumbly and grayish. Variation at a single gene determines which kind of earwax you have; the allele for wet earwax is dominant over the allele for dry earwax. The allele for dry earwax appears to have originated by mutation in northeastern Asia about 2,000 generations ago, then spread outwards because it was favored by natural selection. It is very common in eastern Asia, becomes much less common towards Europe, and is very rare in Africa. 21

22 Molecular genetics Tomita et al. (2002) used eight Japanese families to determine that the gene for wet/dry earwax is on chromosome 16, near the centromere. Yoshiura et al. (2006) then found the gene responsible: ABCC11 (ATP-binding cassette, subfamily C, member 11). The allele for wet earwax has a G at site 538 of the coding region, which causes a glycine at position 180 in the amino acid sequence; most dry alleles have an A at site 538, coding for arginine. By the law of independent assortment, each pair of alleles segregates into gametes independently Mendel s experiments that followed the inheritance of flower color or other characters focused on only a single character via monohybrid crosses. He conducted other experiments in which he followed the inheritance of two different characters, a dihybrid cross. 22

23 In one dihybrid cross experiment, Mendel studied the inheritance of seed color and seed shape. The allele for yellow seeds (Y) is dominant to the allele for green seeds (y). The allele for round seeds (R) is dominant to the allele for wrinkled seeds (r). Mendel crossed true-breeding plants that had yellow, round seeds (YYRR) with true-breeding plants that has green, wrinkled seeds (yyrr). One possibility is that the two characters are transmitted from parents to offspring as a package. The Y and R alleles and y and r alleles stay together. If this were the case, the F 1 offspring would produce yellow, round seeds. The F 2 offspring would produce two phenotypes in a 3:1 ratio, just like a monohybrid cross. This was not consistent with Mendel s results. An alternative hypothesis is that the two pairs of alleles segregate independently of each other. The presence of one specific allele for one trait has no impact on the presence of a specific allele for the second trait. In our example, the F 1 offspring would still produce yellow, round seeds. However, when the F 1 s produced gametes, genes would be packaged into gametes with all possible allelic combinations. Four classes of gametes (YR, Yr, yr, and yr) would be produced in equal amounts. 23

24 Cross a YYRR x yyrr Y = Yellow peas R = Round y = Green peas r = Wrinkled Show your work and ratios Cross a YYRR x yyrr Y = Yellow peas R = Round y = Green peas r = Wrinkled 1 st find the gametes for each parent R Y Y r y y R r Cross a YYRR x yyrr Y = Yellow peas R = Round y = Green peas r = Wrinkled Y Y R YR YR r y y R YR YR r 24

25 Cross a YYRR x yyrr Y = Yellow peas R = Round y = Green peas r = Wrinkled Y Y R YR YR R YR YR y y r yr yr r yr yr Cross a YYRR x yyrr Y = Yellow peas R = Round y = Green peas r = Wrinkled YR YR YR YR yr yr yr yr Cross a YYRR x yyrr Y = Yellow peas R = Round y = Green peas r = Wrinkled YR YR YR YR yr YyRr YyRr YyRr YyRr yr YyRr YyRr YyRr YyRr yr YyRr YyRr YyRr YyRr yr YyRr YyRr YyRr YyRr 25

26 Cross a YYRR x yyrr Y = Yellow peas R = Round y = Green peas r = Wrinkled Genotype = 100% YyRr Phenotype = 100% Yellow Round Peas Cross a YyRr x YyRr Y = Yellow peas R = Round y = Green peas r = Wrinkled Show your work and ratios 26

27 When sperm with four classes of alleles and ova with four classes of alleles combined, there would be 16 equally probable ways in which the alleles can combine in the F 2 generation. These combinations produce four distinct phenotypes in a 9:3:3:1 ratio. Each character is inherited independently. The independent assortment of each pair of alleles during gamete formation is now called Mendel s law of independent assortment. One other aspect that you can notice in the dihybrid cross experiment is that if you follow just one character, you will observe a 3:1 F 2 ratio for each, just as if this were a monohybrid cross. Coin Toss Lab 27

28 Mendelian inheritance rules of probability Mendel s laws of segregation and independent assortment reflect the same laws of probability that apply to tossing coins or rolling dice. The probability of tossing heads with a normal coin is 1/2. The probability of rolling a 3 with a six-sided die is 1/6, and the probability of rolling any other number is 1-1/6 = 5/6. When tossing a coin, the outcome of one toss has no impact on the outcome of the next toss. Each toss is an independent event, just like the distribution of alleles into gametes. Each time you toss a coin the odds of heads vs tails is the same 50/50 Like a coin toss, each ovum from a heterozygous parent has a 1/2 chance of carrying the dominant allele and a 1/2 chance of carrying the recessive allele. The same odds apply to the sperm. 28

29 We can use the rule of multiplication to determine the chance that two or more independent events will occur together in some specific combination. Compute the probability of each independent event. Then, multiply the individual probabilities to obtain the overall probability of these events occurring together. The probability that two coins tossed at the same time will land heads up is 1/2 x 1/2 = 1/4. Similarly, the probability that a heterogyzous pea plant (Pp) will produce a white-flowered offspring (pp) depends on an ovum with a white allele mating with a sperm with a white allele. This probability is 1/2 x 1/2 = 1/4. The rule of multiplication also applies to dihybrid crosses. For a heterozygous parent (YyRr) the probability of producing a YR gamete is 1/2 x 1/2 = 1/4. We can use this to predict the probability of a particular F 2 genotype without constructing a 16-part Punnett square. The probability that an F 2 plant will have a YYRR genotype from a heterozygous parent is 1/16 (1/4 chance for a YR ovum and 1/4 chance for a YR sperm). The rule of addition also applies to genetic problems. Under the rule of addition, the probability of an event that can occur two or more different ways is the sum of the separate probabilities of those ways. For example, there are two ways that F 1 gametes can combine to form a heterozygote. The dominant allele could come from the sperm and the recessive from the ovum (probability = 1/4). Or, the dominant allele could come from the ovum and the recessive from the sperm (probability = 1/4). The probability of a heterozygote is 1/4 + 1/4 = 1/2. 29

30 We can combine the rules of multiplication and addition to solve complex problems in Mendelian genetics. Let s determine the probability of finding two recessive phenotypes for at least two of three traits resulting from a trihybrid cross between pea plants that are PpYyRr and Ppyyrr. There are five possible genotypes that fulfill this condition: ppyyrr, ppyyrr, Ppyyrr, PPyyrr, and ppyyrr. We would use the rule of multiplication to calculate the probability for each of these genotypes and then use the rule of addition to pool the probabilities for fulfilling the condition of at least two recessive traits. The probability of producing a ppyyrr offspring: The probability of producing pp = 1/2 x 1/2 = 1/4. The probability of producing yy = 1/2 x 1 = 1/2. The probability of producing Rr = 1/2 x 1 = 1/2. Therefore, the probability of all three being present (ppyyrr) in one offspring is 1/4 x 1/2 x 1/2 = 1/16. For ppyyrr: 1/4 x 1/2 x 1/2 = 1/16. For Ppyyrr: 1/2 x 1/2 x 1/2 = 2/16 For PPyyrr: 1/4 x 1/2 x 1/2 = 1/16 For ppyyrr: 1/4 x 1/2 x 1/2 = 1/16 Therefore, the chance of at least two recessive traits is 6/ Mendel discovered the particulate behavior of genes: a review While we cannot predict with certainty the genotype or phenotype of any particular seed from the F2 generation of a dihybrid cross, we can predict the probabilities that it will fit a specific genotype of phenotype. Mendel s experiments succeeded because he counted so many offspring and was able to discern this statistical feature of inheritance and had a keen sense of the rules of chance. 30

31 Mendel s laws of independent assortment and segregation explain heritable variation in terms of alternative forms of genes that are passed along according to simple rule of probability. These laws apply not just to garden peas, but to all other diploid organisms that reproduce by sexual reproduction. Mendel s studies of pea inheritance endure not only in genetics, but as a case study of the power of scientific reasoning using the hypotheticodeductive approach. The relationship between genotype and phenotype is rarely simple The relationship between genotype and phenotype is rarely simple In the 20th century, geneticists have extended Mendelian principles not only to diverse organisms, but also to patterns of inheritance more complex than Mendel described. In fact, Mendel had the good fortune to choose a system that was relatively simple genetically. Each character (but one) is controlled by a single gene. Each gene has only two alleles, one of which is completely dominant to the other. 31

32 The heterozygous F 1 offspring of Mendel s crosses always looked like one of the parental varieties because one allele was dominant to the other. However, some alleles show incomplete dominance where heterozygotes show a distinct intermediate phenotype, not seen in homozygotes. This is not blended inheritance because the traits are separable (particulate) as seen in further crosses. Offspring of a cross between heterozygotes will show three phenotypes: both parentals and the heterozygote. The phenotypic and genotypic ratios are identical, 1:2:1. A clear example of incomplete dominance is seen in flower color of snapdragons. A cross between a white-flowered plant and a red-flowered plant will produce all pink F 1 offspring. Self-pollination of the F 1 offspring produces 25% white, 25% red, and 50% pink offspring. Incomplete and complete dominance are part of a spectrum of relationships among alleles. At the other extreme from complete dominance is codominance in which two alleles affect the phenotype in separate, distinguishable ways. For example, the M, N, and MN blood groups of humans are due to the presence of two specific molecules on the surface of red blood cells. People of group M (genotype MM) have one type of molecule on their red blood cells, people of group N (genotype NN) have the other type, and people of group MN (genotype MN) have both molecules present. 32

33 The dominance/recessiveness relationships depend on the level at which we examine the phenotype. For example, humans with Tay-Sachs disease lack a functioning enzyme to metabolize gangliosides (a lipid) which accumulate in the brain, harming brain cells, and ultimately leading to death. Children with two Tay-Sachs alleles have the disease. Heterozygotes with one working allele and homozygotes with two working alleles are normal at the organismal level, but heterozygotes produce less functional enzymes. However, both the Tay-Sachs and functional alleles produce equal numbers of enzyme molecules, codominant at the molecular level. Dominant alleles do not somehow subdue a recessive allele. It is in the pathway from genotype to phenotype that dominance and recessiveness come into play. For example, wrinkled seeds in pea plants with two copies of the recessive allele are due to the accumulation of monosaccharides and excess water in seeds because of the lack of a key enzyme. The seeds wrinkle when they dry. Both homozygous dominants and heterozygotes produce enough enzymes to convert all the monosaccharides into starch and form smooth seeds when they dry. Because an allele is dominant does not necessarily mean that it is more common in a population than the recessive allele. For example, polydactyly, in which individuals are born with extra fingers or toes, is due to an allele dominant to the recessive allele for five digits per appendage. However, the recessive allele is far more prevalent than the dominant allele in the population. 399 individuals out of 400 have five digits per appendage. 33

34 Dominance/recessiveness relationships have three important points. 1. They range from complete dominance, though various degrees of incomplete dominance, to codominance. 2. They reflect the mechanisms by which specific alleles are expressed in the phenotype and do not involve the ability of one allele to subdue another at the level of DNA. 3. They do not determine or correlate with the relative abundance of alleles in a population. Most genes have more than two alleles in a population. The ABO blood groups in humans are determined by three alleles, I A, I B, and i. Both the I A and I B alleles are dominant to the i allele The I A and I B alleles are codominant to each other. Because each individual carries two alleles, there are six possible genotypes and four possible blood types. Individuals that are I A I A or I A i are type A and place type A oligosaccharides on the surface of their red blood cells. Individuals that are I B I B or I B i are type B and place type B oligosaccharides on the surface of their red blood cells. Individuals that are I A I B are type AB and place both type A and type B oligosaccharides on the surface of their red blood cells. Individuals that are ii are type O and place neither oligosaccharide on the surface of their red blood cells. 34

35 Matching compatible blood groups is critical for blood transfusions because a person produces antibodies against foreign blood factors. If the donor s blood has an A or B oligosaccharide that is foreign to the recipient, antibodies in the recipient s blood will bind to the foreign molecules, cause the donated blood cells to clump together, and can kill the recipient. Fig The genes that we have covered so far affect only one phenotypic character. However, most genes are pleiotropic, affecting more than one phenotypic character. For example, the wide-ranging symptoms of sickle-cell disease are due to a single gene. Considering the intricate molecular and cellular interactions responsible for an organism s development, it is not surprising that a gene can affect a number of an organism s characteristics. 35

36 In epistasis, a gene at one locus alters the phenotypic expression of a gene at a second locus. For example, in mice and many other mammals, coat color depends on two genes. One, the epistatic gene, determines whether pigment will be deposited in hair or not. Presence (C) is dominant to absence (c). The second determines whether the pigment to be deposited is black (B) or brown (b). The black allele is dominant to the brown allele. An individual that is cc has a white (albino) coat regardless of the genotype of the second gene. A cross between two black mice that are heterozygous (BbCc) will follow the law of independent assortment. However, unlike the 9:3:3:1 offspring ratio of an normal Mendelian experiment, the ratio is nine black, three brown, and four white. Fig Some characters do not fit the either-or basis that Mendel studied. Quantitative characters vary in a population along a continuum. These are usually due to polygenic inheritance, the additive effects of two or more genes on a single phenotypic character. For example, skin color in humans is controlled by at least three different genes. Imagine that each gene has two alleles, one light and one dark, that demonstrate incomplete dominance. An AABBCC individual is dark and aabbcc is light. 36

37 A cross between two AaBbCc individuals (intermediate skin shade) would produce offspring covering a wide range of shades. Individuals with intermediate skin shades would be the most likely offspring, but very light and very dark individuals are possible as well. The range of phenotypes forms a normal distribution. Fig Phenotype depends on environment and genes. A single tree has leaves that vary in size, shape, and greenness, depending on exposure to wind and sun. For humans, nutrition influences height, exercise alters build, sun-tanning darkens the skin, and experience improves performance on intelligence tests. Even identical twins, genetic equals, accumulate phenotypic differences as a result of their unique experiences. The relative importance of genes and the environment in influencing human characteristics is a very old and hotly contested debate. The product of a genotype is generally not a rigidly defined phenotype, but a range of phenotypic possibilities, the norm of reaction, that are determined by the environment. In some cases the norm of reaction has no breadth (for example, blood type). Norms of reactions are broadest for polygenic characters. For these multifactorial characters, environment contributes to their quantitative nature. Fig

38 An emphasis on single genes and single phenotypic characters presents an inadequate perspective on heredity and variation. A more comprehensive theory of Mendelian genetics must view organisms as a whole. Phenotype has been used to this point in the context of single characters, but it is also used to describe all aspects of an organism. Genotype can refer not just to a single genetic locus, but also to an organism s entire genetic makeup. An organism s phenotype reflects its overall genotype and unique environmental history. These traits include: Ability to taste phenylthiocarbamide Albinism (recessive) Blood type Brachydactyly (Shortness of fingers and toes) Cleft chin (dominant) Cheek dimples (dominant) Free (dominant) or attached (recessive) earlobes Wet (dominant) or dry (recessive) earwax Face freckles (dominant) Hitchhiker's thumb (recessive) Sexdactyly (Six fingers/toes) Sickle-cell trait (also considered co-dominant) Widow's peak (dominant) Mendelian Inheritance in Humans 1. Pedigree analysis reveals Mendelian patterns in human inheritance 2. Many human disorders follow Mendelian patterns of inheritance 3. Technology is providing new tools for genetic testing and counseling 38

39 While peas are convenient subjects for genetic research, humans are not. The problem with humans is the time between generations is too long, fecundity too low, and breeding experiments are unacceptable to society. Yet, humans are subject to the same rules regulating inheritance as other organisms. So in order to study human genetics we have to rely on new techniques in molecular biology (DNA testing) Pedigree analysis reveals Mendelian patterns in human inheritance To get around the problems related to experimenting on people biologists have to work backwards. Rather than manipulate mating patterns of people, geneticists analyze the results of matings that have already occurred. In a pedigree analysis, information about the presence/absence of a particular phenotypic trait is collected from as many individuals in a family as possible and across generations. The distribution of these characters is then mapped on the family tree. 39

40 A Simple Human Pedigree For example, the occurrence of widows peak (W) is dominant to a straight hairline (w). Pedigrees allow us to show genotypic or phenotypic information in a much easier to understand way. For example, try to imagine the movement of genes in a family that would result in an individual in the F3 generation lacking a widow s peak even if both her parents have widow s peaks. What could her grandparents be? If we draw a pedigree solving this problem becomes much easier. 40

41 If some siblings in the second generation lack a widow s peak and one of the grandparents (first generation) also lacks one, then we know the other grandparent must be heterozygous and we can determine the genotype of almost all other individuals. We can use the same family tree to trace the distribution of attached earlobes (f), a recessive characteristic. Individuals with a dominant allele (F) have free earlobes. Some individuals may be ambiguous, especially if they have the dominant phenotype and could be heterozygous or homozygous dominant. A pedigree can help us understand the past and to predict the future. We can use the normal Mendelian rules, including multiplication and addition, to predict the probability of specific phenotypes. For example, these rules could be used to predict the probability that a child with WwFf parents will have a widow s peak and attached earlobes. The chance of having a widow s peak is 3/4 (1/2 [WW] + 1/4 [Ww]). The chance of having attached earlobes is 1/4 [ff]. This combination has a probability of 3/4 + 1/4 = 3/16. 41

42 Marfan syndrome is a genetic connective tissue disorder often characterized by unusually long limbs, great stature or long toes or fingers in proportion to height. Marfan syndrome is an autosomal dominant disorder that has been linked to a mutation in the FBN1 gene on chromosome 15 Draw a Punnett square that shows the probability of having offspring with Marfan is the father is heterozygous and the mother is homozygous recessive for the trait. Dad is heterozygous and mom is homozygous recessive Ff x ff f f F Ff Ff f ff ff Genotypic Ratio 2 Ff 2 ff Phenotypic Ratio 2 Marfan 2 Without Marfan Complete this Human Pedigree using the information about Marfan Shaded circles are positive for the trait 42

43 Complete this Human Pedigree using the information about Marfan Shaded circles are positive for the trait Ff ff ff Ff ff ff ff Ff ff While heterozygotes may have no clear phenotypic effects, they are carriers who may transmit a recessive allele to their offspring. Most people with recessive disorders are born to carriers with normal phenotypes. Two carriers have a 1/4 chance of having a child with the disorder, 1/2 chance of a carrier, and 1/4 free. Genetic disorders are not evenly distributed among all groups of humans. This results from the different genetic histories of the world s people during times when populations were more geographically (and genetically) isolated. 43

44 Non-disjunction occurs when chromosomes in the developing gamete (sex cell) fail to separate during one of the divisions of meiosis. The result is a sperm or egg cell with either an additional chromosome, or one that lacks one chromosome. If this sex cell combines with one from the opposite sex, the resulting fetus will have cells with an extra chromosome (or be one short). Generally, such fetus' will not develop properly and we would say that the resulting baby would have genetic disorder (such as Down Syndrome). 44

45 Most birth defects are not caused by nondisjunction as it is very rare for successful pregnancy to result after nondisjunction -- only with smallest chromosomes or sex chromosomes. Even then, almost always leads to developmental abnormalities, some degree of mental retardation. Examples of Genetic Disorders caused by Nondisjunction: 1. Down's Syndrome: 47 chromosomes with 3 #21 chromosomes. 2. Triple-X Syndrome: 47 chromosomes caused by 3 X chromosomes. 3. Klinefelter's Syndrome: 47 chromosomes caused by 2 X chromosomes and 1 Y chromosomes. 4. Turner's Syndrome: 45 chromosomes with 1 X chromosome (caused by the absence of one of the X chromosomes or a Y chromosome). Turner's syndrome: One X. A rare chromosomal disorder of females (1 in 2500) characterized by short stature and the lack of sexual development at puberty. 45

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